Analysis of catalytic determinants of diaminopimelate and ornithine decarboxylases using alternate substrates

Emily J. Fogle, Michael D. Toney

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Diaminopimelate decarboxylase (DAPDC) and ornithine decarboxylase (ODC) are pyridoxal 5′-phosphate dependent enzymes that are critical to microbial growth and pathogenicity. The latter is the target of drugs that cure African sleeping sickness, while the former is an attractive target for antibacterials. These two enzymes share the (β/α)8 (i.e., TIM barrel) fold with alanine racemase, another pyridoxal 5′-phosphate dependent enzyme critical to bacterial survival. The active site structural homology between DAPDC and ODC is striking even though DAPDC catalyzes the decarboxylation of a D stereocenter with inversion of configuration and ODC catalyzes the decarboxylation of an L stereocenter with retention of configuration. Here, the structural and mechanistic bases of these interesting properties are explored using reactions of alternate substrates with both enzymes. It is concluded that simple binding determinants do not control the observed stereochemical specificities for decarboxylation, and a concerted decarboxylation/proton transfer at Cα of the D stereocenter of diaminopimelate is a possible mechanism for the observed specificity with DAPDC.

Original languageEnglish (US)
Pages (from-to)1113-1119
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1814
Issue number9
DOIs
StatePublished - Sep 2011

Keywords

  • Decarboxylase
  • Decarboxylation
  • Enzyme mechanisms
  • Pyridoxal 5′phosphate
  • Reaction specificity
  • TIM barrel

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

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